ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.2474A>G (p.Asn825Ser) (rs104895467)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000280478 SCV000329195 uncertain significance not provided 2016-03-14 criteria provided, single submitter clinical testing The N852S variant in the NOD2 gene has been reported in several publications as a rare risk allele associated with Crohn disease in the Ashkenazi Jewish population (Tukel et al., (2004); King et al. (2006); Rivas et al., (2011); Zhang W et al., 2013). The NHLBI ESP Exome Sequencing Project reports N852S was observed with a frequency of 0.11% in 10/8600 alleles from individuals of European background, indicating it may be a rare (benign) variant in this population. The N852S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N852S in NOD2 as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000281894 SCV000397287 likely benign Inflammatory bowel disease 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000336827 SCV000397288 likely benign Blau syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000638061 SCV000759541 risk factor Blau syndrome; Inflammatory bowel disease 1 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 852 of the NOD2 protein (p.Asn852Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs104895467, ExAC 0.2%) including at least one homozygous individual. In a large association analysis involving over 40,000 cases and controls (PMID: 21983784), individuals who carried this variant had a significantly increased risk of Crohn's disease (OR=2.47, 95% CI=1.55-3.93). ClinVar contains an entry for this variant (Variation ID: 97856). Experimental studies have shown that while this missense change does not interfere with normal membrane localization, it impairs MDP-induced NF-kB activation (PMID: 21983784). In summary, this is a frequently observed variant that is associated with an approximately 2.5-fold increased risk for developing Crohn's disease.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000336827 SCV000116244 not provided Blau syndrome no assertion provided not provided

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